The heart active glycoside hellebrin is contained in the roots of the Helleborus species. It is of increased therapeutic interest because of its intermediate position between Stropanthus and Scilla glycosides.
It is known that a glycoside acting in a manner similar to digitalis can be recovered from Helleborus niger by treating aqueous Helleborus with carbon, the carbon adsorbate extracted with organic solvents and the extract obtained subjected to a further purification (German Pat. No. 605,073). The carbon treatment can also precede a lead precipitation wherein the excess lead is removed with phosphate (Helv. Chim. Acta 26, 1353 (1943) or with sulfate (Farmacia (Bucharest) P 407 (1959). This process is not satisfactory.
The disadvantages of the adsorptive precipitation are avoided according to a new process if Helleborus extract is treated successively with different solvents (Czechoslovakian Pat. No. 101,577). This process, however, not only requires a large expenditure of solvents but reworking has shown that as a rule the process does not lead to crystallizable hellebrin.
There has also been described a chromatographic purification of Helleborus extract on aluminum oxide in combination with a preceding lead precipitation (Med. prom. SSR 18, 12 (1964) or without such pretreatment (Planta med. 9, 64 (1961)). The yield of hellebrin, however, only amounts to 0.04%.
More favorable yields are obtained by chromatography or silica gel (Z. Naturforschg. 20b, 707(1965); Acta Pharm. Jug. 17, 29 (1967)). In the previously used silica gels, however, it is a matter of using finely divided silica gels (particle size 0.01 to 0.04 mm, which only permit moderate speeds. Also the capacity of silica gel columns generally is only half as much as that of alumina columns of equal size. Thus this method of separation up to now has been suited only for the recovery of small amounts of hellebrin.
Newer processes operate with a coarse particle silica gel having a particle size of 0.15 to 10 mm (German Pat. Nos. 2,038,110 and 2,123,535 and related Isaac U.S. Pat. No. 3,904,598 and Isaac U.S. Pat. No. 3,912,716. The entire disclosure of the two Isaac U.S. patents is hereby incorporated by reference and relied upon.). In this case there is employed an extract, which for example had been obtained by extraction of a hellebrin containing drug with chloroform-ethanol (2:1 by volume), whereby a very large amount of this extraction agent is required and this extraction furthermore is very long, for example 5 days.